乙型肝炎病毒YMDD变异株的检测及临床意义

Detection and Clinical Significance of HBV YMDD Mutation

目的:建立乙型肝炎病毒P区基因直接测序方法,进一步了解口服拉米夫定的慢性乙型肝炎患者HBVP区发生YMDD变异的情况,并探讨其相关影响因素。方法:应用聚合酶链反应(PCR)扩增HBV DNAP基因区,通过直接测序方法与Genebank标准序列对比,对107例慢性乙肝(CHB)患者血清进行P区测序。结果:107例慢性乙肝患者YMDD变异率为32.7%,其中YIDD变异17例,YVDD变异15例,混合变异3例。YMDD未变异组治疗前谷丙转氨酶(ALT)水平显著高于变异者;而YMDD变异组治疗前HBV DNA含量显著高于未变异组;YMDD未变异组与变异组之间治疗前的患者性别、年龄和HBeAg状态等方面差异无统计学意义。结论:HBV YMDD变异可能与患者治疗前ALT水平和HBV DNA含量有一定关系,而与患者的性别、年龄和血清HBeAg状态无关。

Objective： To establish a direct gene sequencing method of HBV DNA P gene and discuss YMDD mutation of HBV DNA P gene in chronic hepatitis B patients and related factors. Methods： HBV DNA P genes were amplified by PCR and HBV YMDD mutations were identified by direct sequence compared with Genebank standard sequence. HBV P gene sequence analysis was conducted in 107 chronic hepatitis B （CHB） patients. Results： YMDD mutation, rate was 32.7% in 107 chronic hepatitis B patients including YIDD mutation in 17, YVDD mutation in 15 and multi-mutations in 3. Serum ALT level before therapy in patients without YMDD mutation was higher than those in patients with YMDD mutation, and HBV DNA level in pretreatment patients without YMDD mutation was much higher than those in YMDD mutation patients. There was no significant difference between the pretreatment patients without YMDD mutation and with YMDD mutation in sex, age and the state of HBeAg. Conclusion： HBV YMDD mutation may be related to ALT and HBV DNA level before treatment and not related to sex, age and the state of HBeAg.